Homeodomain Interacting Protein Kinase 2-Modified Rat Spinal Astrocytes Affect Neurofunctional Recovery After Spinal Cord Injury

Abstract

Background: Spinal cord injury (SCI) is regarded as an acute neurological disorder, and astrocytes play a role in the progression of SCI. Objective: Herein, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2)- modified rat spinal astrocytes in neurofunctional recovery after SCI. Methods: Rat spinal astrocytes were cultured, isolated, and then identified through microscopic observation and immunofluorescence staining. Astrocytes were infected with the adenovirus vector overexpressing HIPK2 for modification, and proliferation and apoptosis of astrocytes were examined using Cell Counting Kit-8 method and flow cytometry. SCI rat models were established and treated with astrocytes or HIPK2-modified astrocytes. Subsequently, rat motor ability was analyzed via the Basso-Beattie-Bresnahan (BBB) scoring and inclined-plane test, and the damage to spinal cord tissues and neuronal survival were observed via Hematoxylin-eosin staining and Nissl staining. The levels of HIPK2, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nuclear factor erythroid 2- related transcription factor 2 (Nrf2)/antioxidant response element (ARE) pathway-related proteins were detected. Results: Rat spinal astrocytes were harvested successfully. HIPK2 overexpression accelerated the proliferation and repressed the apoptosis of rat spinal astrocytes. Rat spinal astrocytes treatment increased BBB points and the maximum angle at which SCI rats remained stable, ameliorated damage to spinal cord tissues, increased the number of neurons, and attenuated neural damage and inflammation, while the treatment of HIPK2-modified rat spinal astrocytes imparted more pronounced effects to the neurofunctional recovery of SCI rats. Meanwhile, HIPK2-modified rat spinal astrocytes further activated the Nrf2/ARE pathway. Conclusion: HIPK2-modified rat spinal astrocytes facilitated neurofunctional recovery and activated the Nrf2/ARE pathway after SCI.